文章：

恶性血液病：处于免疫治疗创新的前沿

Haematological malignancies: at the forefront of immunotherapeutic innovation

原文发布日期：2015-03-19

DOI: 10.1038/nrc3907

类型: Review Article

开放获取: 否

要点：

1. The impressive potency of novel cancer immunotherapies has refocused attention on this class of agents for both solid and haematological cancers, and the robust experience of immunotherapeutic efforts specifically within haematological malignancies offers insights germane to the development of these strategies.
2. From adoptive cellular therapy and antibody-based therapies to active cancer vaccination, early investigations in the blood malignancies provided both initial proofs of principles and informative testing grounds for agents such as allogeneic haematopoietic stem cell transplantation (allo-HSCT), donor lymphocyte infusion (DLI) and rituximab.
3. Unique features of haematological malignancies that enable the development of immunotherapies include their well-known immune responsiveness, ease of tissue sampling to distinguish malignant from normal cells by surface marker expression, the ability to directly examine immune-based antitumour responses after allo-HSCT and DLI, and their shared sites of origin with normal immune counterparts.
4. Lymphoid and myeloid malignant cells subvert physiological immune programmes both to directly drive cancer growth and to indirectly recruit an inflammatory, immune-supportive infiltrate.
5. Clinical and laboratory investigations in haematological malignancies have suggested four major nodes of potential vulnerability in the cancer–immune relationship: direct targeting of surface tumour antigens; boosting immune effector number and function; activating tumour antigen-specific immunity; and overcoming inhibitory immune suppression.
6. An appreciation of the coordination among distinct cells during an effective immune response suggests a multi-pronged combinatorial strategy for inducing potent antitumour immunity; indeed, recent clinical evidence from trials in haematological malignancies supports this paradigm. Moreover, it is becoming increasingly evident that evaluation of both leukaemic and infiltrating immune cells at the site of disease is important to identify biomarkers of immunotherapeutic response and resistance, which in turn enable selection of appropriate treatment options.

要点翻译：

1. 新型癌症免疫疗法的显著疗效使这类药物在实体瘤和血液肿瘤领域重新成为关注焦点，而血液系统恶性肿瘤中免疫治疗获得的丰富经验为这类策略的开发提供了重要借鉴。
2. 从过继性细胞疗法、抗体药物到主动性癌症疫苗，血液系统恶性肿瘤的早期研究既验证了基本原理，也为异基因造血干细胞移植、供者淋巴细胞输注和利妥昔单抗等制剂提供了重要的试验场。
3. 血液系统恶性肿瘤具有若干独特性质，能促进免疫疗法的开发：公认的免疫应答性、通过表面标志物区分恶性与正常细胞的便捷组织取样、异基因造血干细胞移植和供者淋巴细胞输注后直接检测免疫抗肿瘤反应的能力，以及与正常免疫细胞同源的发生部位。
4. 淋巴和髓系恶性细胞通过颠覆生理性免疫程序，直接驱动癌症进展并间接招募炎症性免疫支持性浸润细胞。
5. 血液系统恶性肿瘤的临床与实验室研究揭示了癌症-免疫关系中四个关键的潜在薄弱环节：表面肿瘤抗原的直接靶向；免疫效应细胞数量与功能的增强；肿瘤抗原特异性免疫的激活；抑制性免疫逃逸机制的克服。
6. 对有效免疫反应中不同细胞间协同作用的理解，提示可采用多管齐下的组合策略诱导强效抗肿瘤免疫；血液系统恶性肿瘤的最新临床试验证据也支持这一范式。此外，越来越多证据表明通过对病灶部位白血病细胞和浸润免疫细胞的评估，可识别免疫治疗应答与抵抗的生物标志物，进而为选择合适的治疗方案提供依据。

英文摘要：

The recent successes of cancer immunotherapies have stimulated interest in the potential widespread application of these approaches; haematological malignancies have provided both initial proofs of concept and an informative testing ground for various immune-based therapeutics. The immune-cell origin of many of the blood malignancies provides a unique opportunity both to understand the mechanisms of cancer immune responsiveness and immune evasion, and to exploit these mechanisms for therapeutic purposes.

摘要翻译： 

癌症免疫疗法的近期成功激发了人们将这些方法广泛应用的兴趣；血液系统恶性肿瘤不仅提供了最初的验证范例，也成为各种基于免疫的治疗策略的重要试验场。许多血液恶性肿瘤起源于免疫细胞，这为理解癌症免疫应答与免疫逃逸机制，以及利用这些机制进行治疗提供了独特机会。

原文链接：

Haematological malignancies: at the forefront of immunotherapeutic innovation